University of Zurich
A Versatile “Synthesis Tag” for Chemical Protein Synthesis
SESSION 9: PEPTIDE SYNTHETIC METHODS & GREEN CHEMISTRY APPROACHES
Wednesday, June 28, 2023, at 10:00 am - 10:25 am
Solid-phase peptide synthesis, SPPS, has been a standard method for chemical protein production for the past 60 years, but its outcome can be highly dependent on the peptide sequence synthesized. One issue that often arises is the aggregation of growing peptide chains, which can lead to incomplete couplings, or "difficult sequences”. Previous research into this sequence-dependent phenomenon was limited by the lack of high-throughput analytical methods, thus impeding systematic analysis. While flow-based SPPS allows for aggregation detection, it has so far not led to the development of tools for its suppression.
Analogous to existing "solubility tags," which assist with the often-observed solubility issues of peptides, we set out to develop a "synthesis tag." Analysis of various parameters affecting aggregation, as well as the development of a synthesis tag, will be presented in the context of chemical protein synthesis. The tag significantly improves synthesis outcomes in flow- and batch-SPPS for various aggregating peptide and protein sequences.
Nina Hartrampf, nee Vrielink, was born in Germany in 1987. She received a Bachelor’s degree in Chemistry and Biochemistry from the Ludwig-Maximilians-Universität München in 2010. During her Master’s studies in Chemistry she was a visiting researcher in the group of Prof. Edward Tate working on peptide-drug conjugates for the modulation of protein-protein interactions. After graduating with honors from Ludwig-Maximilians-Universität München in 2013, she joined the group of Prof. Dirk Trauner for her graduate studies, where she accomplished the total synthesis of the alkaloid stephadiamine. In the context of this synthesis she was a visiting researcher in the group of Prof. Brian Stoltz at the California Institute of Technology and received additional training in asymmetric catalysis. During her PhD she was supported by an Otto-Bayer Fellowship and a fellowship of the Deutsche Telekom Stiftung. After graduating summa cum laude in 2017, she joined the group of Prof. Bradley L. Pentelute at Massachusetts Institute of Technology in 2018. Her postdoctoral work focused on the rapid high-fidelity synthesis of proteins using automated flow chemistry. Additional work included reaction development in flow, development of peptide-drug conjugates for targeted delivery and the synthesis of nonribosomal peptides. In 2019, her work was acknowledged with a Bert Schram Award of the American Peptide Society, and in 2021 she was awarded the Bachem Award for Peptide Science.
In March 2020, Nina joined the Department of Chemistry at the University of Zurich as Assistant Professor for “Next Generation Synthesis,” tenure track.